DESCRIPTION(Adapted from applicant's abstract): The neurotransmitter substance P (SP) is implicated in a number of neurological disorders, yet the regulation of the SP-encoding preprotachykinin (PPT) gene is poorly understood. Using organotypic brain slice cultures, particle-mediated gene transfection, quantitative confocal microscopic analysis and site specific mutagenesis, we will identify the gene regulatory elements mediating neuron-specific expression and the response to dopamine and other stimuli. For the first time, PPT promoter activity will be quantified within single, living PPT-expressing neurons. Ultimately, the ability to modify substance P neurotransmission at the transcriptional level may constitute a novel therapeutic target for the treatment of Parkinson's disease and other movement disorders, chronic pain, anxiety and depression, addiction and other neuropsychiatric disorders.